Efficacy Study of Two Treatments in the Remission of Vasculitis

Brief Title

Efficacy Study of Two Treatments in the Remission of Vasculitis

Official Title

MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis

Brief Summary

      Study of the efficacy of rituximab for maintenance treatment in systemic ANCA-associated
      vasculitis: prospective, multicenter, controlled, randomized comparative study of rituximab
      versus azathioprine
    

Detailed Description

      Randomized, controlled, national, multicenter, prospective study to compare between
      azathioprine (conventional therapy) and rituximab in patients with systemic ANCA-associated
      vasculitis, in remission (achieved with an induction treatment combining corticosteroids and
      an immunosuppressant, mainly intravenous pulses of cyclophosphamide, and plasma exchanges
      and/or polyvalent immunoglobulins when indicated) after the first flare of the disease (new
      diagnosis) or after a relapse. It is planned to stratify patients by first flare (66% of the
      patients) or relapse (33% of the patients). Patients complying with the inclusion criteria
      may be included when they are in remission from their vasculitis. Patients who have already
      received biologics (antiCD20, antiTNFα) will not be included. Patients will be included at
      the time of remission and then randomized. They will receive maintenance treatment by
      azathioprine for 18 months or a rituximab infusion every 6 months until month 18 (i.e. a
      total of 4 infusions), at the dose of 375 mg/m2 (maximum dosage, 500 mg). ANCA status and
      CD19+ lymphocyte count will be monitored but will not be used to adjust therapy. After the 18
      month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy,
      patients will be followed for an additional 10 month period. Patients with Wegener's
      granulomatosis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Number of major relapse (BVAS>10) in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)

Secondary Outcome

 To assess the number of adverse events and their severity in each group

Condition

Wegener Granulomatosis

Intervention

Rituximab

Study Arms / Comparison Groups

 1

Description:  Experimental drug = rituximab for maintenance

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

117

Start Date

October 2008

Completion Date

June 2013

Primary Completion Date

March 2013

Eligibility Criteria

        Inclusion Criteria:

          -  Wegener's granulomatosis Or microscopic polyangiitis complying Or kidney-limited
             disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at
             the time of diagnosis or relapse, and at remission.

          -  Who have achieved remission using a treatment combining corticosteroids and an
             immunosuppressive agent according to current French guideline, including
             corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is
             allowed, according to the current French guidelines, as well as plasma exchanges
             and/or IV immunoglobulins).

          -  Interval of 1 month between the end of the immunosuppressant treatment and the
             randomization time

          -  Age > 18 years and < 75 years when the diagnosis is confirmed.

          -  Informed and having signed the consent form to take part in the study.

        Exclusion Criteria:

          -  Other systemic vasculitis

          -  Secondary vasculitis (following neoplastic disease or an infection in particular)·

          -  Induction treatment with a regimen not corresponding to that recommended in France.

          -  Patient who has not achieved remission.·

          -  Patient who has already received a treatment by biological agents (monoclonal antibody
             - antiCD20 or antiTNFα).

          -  Incapacity or refusal to understand or sign the informed consent form.

          -  Incapacity or refusal to adhere to treatment or perform the follow-up examinations
             required by the study. Non-compliance·

          -  Allergy, documented hypersensitivity or contraindication to the study medication
             (cyclophosphamide, corticosteroids, azathioprine, rituximab),

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies.

          -  Patients receiving allopurinol cannot be included if the allopurinol must absolutely
             be maintained.

          -  Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of
             contraception throughout the duration of immunosuppressive treatment up to 1 year
             after the last infusion of rituximab

          -  Infection by HIV, HCV or HBV

          -  Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV
             infection, etc.).

          -  Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8,
             HCV, HIV, tuberculosis).

          -  Progressive cancer or malignant blood disease diagnosed during the 5 years before the
             diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or
             those cured of a cancer or a malignant blood disorder for more than 5 years and not
             taking any antineoplastic agents for more than 5 years may be included.

          -  patients presenting a systemic disease receiving protocolized treatments
             (azathioprine, rituximab) which could have unexpected and inappropriate side effects.

          -  Participation in another clinical research protocol during the 4 weeks before
             inclusion.

          -  Any medical or psychiatric disorder which, in the investigator's opinion, may prevent
             the administration of treatment and patient follow-up according to the protocol,
             and/or which may expose the patient to a too greater risk of an adverse effect.

          -  No social security

          -  Churg and Strauss syndrome

          -  viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks
             before the inclusion

          -  history of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the
             first year before the inclusion

          -  History of chronic and severe or recurrent infection or history of preexisting disease
             predisposing to severe infection

          -  Severe immunodepression

          -  Administration of live vaccine in the four weeks before inclusion

          -  severe chronic obstructive pulmonary diseases (VEMS < 50 % or dyspnea grade III)

          -  chronic heart failure stade III and IV (NYHA)

          -  History of recent acute coronary syndrome
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Loic Guillevin, MD, PhD, , 

Location Countries

France

Location Countries

France

NCT ID

NCT00748644

Organization ID

P 070703

Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris

Study Sponsor

Loic Guillevin, MD, PhD, Study Director, French Vasculitis Study Group

Verification Date

January 2012